Structure-based design of high affinity streptavidin binding cyclic peptide ligands containing thioether crosslinks.

Katz, B.A.; Johnson, Charles R.; Cass, Robert

doi:10.1021/ja00138a008

Cited by 29 publications

(28 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peptide Synthesis-Peptides for crystallography, FSHPQNT, cycloAc-[CHPQGPPC]-NH 2 , cyclo-Ac-[CHPQFC]-NH 2 , and cyclo-[5-S-valeramide-HPQGPPC]K-NH 2 were synthesized as described (6,13,22). For BIAcore analysis, corresponding peptides Ac-AEFSHPQNTIEGRK-NH 2 , cyclo-Ac-AE[CHPQGPPC]IEGRK-NH 2 , cyclo-Ac-AE[CHPQFC]-IEGRK-NH 2 and cyclo-[5-S-valeramide-HPQGPPC]K-NH 2 were synthesized as described (6,22).…”

Section: Methodsmentioning

confidence: 99%

“…For BIAcore analysis, corresponding peptides Ac-AEFSHPQNTIEGRK-NH 2 , cyclo-Ac-AE[CHPQGPPC]IEGRK-NH 2 , cyclo-Ac-AE[CHPQFC]-IEGRK-NH 2 and cyclo-[5-S-valeramide-HPQGPPC]K-NH 2 were synthesized as described (6,22). The first three of these are longer than the corresponding ones for crystallography; they contains N-terminal AE sequence and C-terminal IEGRK for reasons independent of the present study (6).…”

Section: Methodsmentioning

confidence: 99%

“…These structures enabled the successful design of cyclic peptide ligands conformationally constrained with designed thioether cross-links (22), of streptavidin dimerizing peptide ligands (19 -21), and of a streptavidinbinding small molecule ligand (12).…”

mentioning

confidence: 99%

“…The -NH 2 at pH 2.5, 2.9 and 3.7, and FSHPQNT at pH 4.0. Several structures are determined in two space groups, I222 and I4 1 22. The structures of the complexes are compared with those previously determined at other pH values.…”

mentioning

confidence: 99%

See 3 more Smart Citations

In Crystals of Complexes of Streptavidin with Peptide Ligands Containing the HPQ Sequence the pK of the Peptide Histidine Is Less than 3.0

Katz

Cass

1997

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Screening of peptide libraries either displayed on phage by molecular biology or produced by combinatorial chemical synthesis is an effective method for discovery of peptide ligands for diverse protein targets. Owing to the remarkably high stability and high affinity of streptavidin for its natural ligand biotin (K d ϳ10 Ϫ15 M) (1), together with widespread bioanalytical, diagnostic, and therapeutic applications (2-5), this protein has been extensively used to develop and validate such screening methodologies. High affinity unnatural ligands have been discovered by screening linear (6 -11) and cyclic (6) peptide libraries. Streptavidin also provides an ideal paradigm for probing the structural basis of high affinity protein-ligand interactions (12-16) and for introducing or improving properties by protein engineering (2, 17, 18). Finally, the high resolution crystal structures of apostreptavidin and of streptavidin-ligand complexes provide a powerful basis for developing structure-based ligand design strategies (12, 19 -23).Recently we described the structures of streptavidin-bound linear and cyclic peptide ligands containing the HPQ sequence (13) discovered by phage display and probed the structural basis for the higher affinities of the cyclic ligands compared with the corresponding linear ones. These structures enabled the successful design of cyclic peptide ligands conformationally constrained with designed thioether cross-links (22), of streptavidin dimerizing peptide ligands (19 -21), and of a streptavidinbinding small molecule ligand (12).The binding to streptavidin and avidin of certain small molecule and peptide ligands is pH-dependent. The affinities for avidin of biotin derivatives, 2-iminobiotin and diaminobiotin, decrease dramatically as the pH is lowered (24), as does the affinity for streptavidin of a linear peptide discovered by phage display, FSHPQNT (25). The extent of topochemical catalysis of disulfide formation and the resulting dimerization of designed streptavidin-bound HPQ-containing ligands whose thiols are presented next to one another in the crystal lattice also depend on pH (20).Determination of the pH dependence of ligand binding or of changes in properties incurred by ligand binding often yields insight into the mode of action (26 -28) or mechanism of binding (29 -36) in biological and chemical processes. Appraisal of the ionization states of groups in a protein-bound ligand or at the ligand binding site of the protein target may reveal some of the determinants of high affinity binding crucial for structurebased ligand design. To this end we determine the pH dependences of binding to streptavidin of linear and cyclic peptide ligands containing the HPQ sequence and probe the structural basis for the dependences through crystallographic determination of complexes at multiple pH values. The affinities for streptavidin at pH 3. 0, 4.0, 5.0, 6.0, 6.2, 6.4, 7.0, 7.3, 8.0, and 9.3 of linear Ac-AEFSHPQNTIEGRK-NH 2 , cyclo-Ac-AE[CH-PQGPPC]IEGRK-NH 2 , cyclo-Ac-AE[CHPQFC]IEGRK-NH 2 , and cyc...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

In Crystals of Complexes of Streptavidin with Peptide Ligands Containing the HPQ Sequence the pK of the Peptide Histidine Is Less than 3.0

Katz

Cass

1997

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Streptavidin, a tetrameric protein with a molecular mass of 13,200 Da/subunit produced by Streptomyces avidinii, functions as an antibiotic by binding the vitamin biotin with the highest affinity known for a noncovalent protein-ligand interaction, K d ϳ10 Ϫ15 M (6). This remarkable affinity forms the basis for many bioanalytical applications (7)(8)(9)(10), as well as a paradigm for studying the structural basis of high affinity protein-ligand interactions (11)(12)(13)37), and for applying structure-based ligand design strategies (14,15).…”

mentioning

confidence: 99%

Topochemical Catalysis Achieved by Structure-based Ligand Design

Katz

Cass

Liu

et al. 1995

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Dimerization is a trigger for many important biological processes (1-4). Recently we described a structure-based design strategy for the preparation of ligands that dimerize receptors by topochemistry (5), which involves a chemical reaction mediated by holding reactants in close proximity and in productive orientations on a protein or crystal scaffold.The strategy for preparation by topochemistry of receptor dimerizing molecules is as follows. First, a protein ligand for a receptor monomer is developed by structure-based design or discovered by screening. The three-dimensional structure of the protein-ligand complex is then determined by crystallography. Ligating groups of the appropriate length and orientation are then introduced at sites in the ligand in a region distinct from the binding motif. Dimerization of two such ligands, each bound on a receptor monomer of a native receptor dimer complex, is directed by the receptor monomers, which present the reactive ligating groups of the ligands next to one another. A ligand dimer capable of dimerizing the receptor to produce a native or native-like receptor dimer is thus prepared by topochemistry.This strategy for preparing a receptor-dimerizing ligand was demonstrated (5) with streptavidin using a high affinity cyclic peptide ligand, cyclo-Ac-[CHPQGPPC]-NH 2 , with a K d of 670 nM at pH 7.3, discovered by screening phage libraries against the streptavidin target (36). Streptavidin, a tetrameric protein with a molecular mass of 13,200 Da/subunit produced by Streptomyces avidinii, functions as an antibiotic by binding the vitamin biotin with the highest affinity known for a noncovalent protein-ligand interaction, K d ϳ10 Ϫ15 M (6). This remarkable affinity forms the basis for many bioanalytical applications (7-10), as well as a paradigm for studying the structural basis of high affinity protein-ligand interactions (11-13, 37), and for applying structure-based ligand design strategies (14, 15).In streptavidin, there are four binding sites, one per subunit. In I222 crystals of streptavidin, one crystallographically equivalent pair, site 1 and site 1Ј, is near a crystallographic 2-fold axis; the other pair, site 2 and site 2Ј, is not. When bound to I222 crystals of streptavidin, the intramolecular disulfide bonds of neighboring cyclo-Ac-[CHPQGPPC]-NH 2 monomers bound at site 1, presented next to one another, undergo disulfide interchange. Thus a C2-symmetric peptide dimer adopting the symmetry of the crystal is produced with two intermolecular disulfide bonds passing through the 2-fold axis. A doubleheaded streptavidin dimerizing agent is thereby prepared by topochemistry. Concomitant with peptide dimerization is the dimerization of the associated bound streptavidin tetramers. We determined the crystal structure of the protein-peptide dimer complex and demonstrated by HPLC 1 and mass spectrometry that streptavidin crystals of space group I222 mediate the dimerization (5).Although I222 streptavidin crystals mediate the disulfide interchange reaction between neighboring...

show abstract

Structural consensus in ligand-protein docking identifies recognition peptide motifs that bind streptavidin

1997

View full text Add to dashboard Cite

Computational structure prediction of streptavidin-peptide complexes for known recognition sequences and a number of random di-, tri-, and tetrapeptides has been conducted, and mechanisms of peptide recognition with streptavidin have been investigated by a new computational protocol. The structural consensus criterion, which is computed from multiple docking simulations and measures the accessibility of the dominant binding mode, identifies recognition motifs from a set of random peptide sequences, whereas energetic analysis is less discriminatory. The predicted conformations of recognition tripeptide and tetrapeptide sequences are also in structural harmony and composed of peptide fragments that are individually unfrustrated in their bound conformation, resulting in a minimally frustrated energy landscape for recognition peptides.

show abstract

Structure-based design of high affinity streptavidin binding cyclic peptide ligands containing thioether crosslinks.

Cited by 29 publications

References 0 publications

In Crystals of Complexes of Streptavidin with Peptide Ligands Containing the HPQ Sequence the pK of the Peptide Histidine Is Less than 3.0

In Crystals of Complexes of Streptavidin with Peptide Ligands Containing the HPQ Sequence the pK of the Peptide Histidine Is Less than 3.0

Topochemical Catalysis Achieved by Structure-based Ligand Design

Structural consensus in ligand-protein docking identifies recognition peptide motifs that bind streptavidin

Contact Info

Product

Resources

About